Human influenza epidemics occur almost every year around the world while influenza viruses mutate. In addition, human influenza pandemics occur roughly every several tens of years, causing several millions to several tens of millions of deaths. It is well known that highly pathogenic avian H5N1 influenza virus, now causing outbreaks among poultry mainly in Asian countries, is feared as a cause of the next pandemic. At present, to prevent damages to humans caused by influenza viruses, vaccination or drugs are used. However, during an epidemic caused by a novel influenza virus, it is extremely difficult to prevent infections with vaccines, which require epidemic assessment, and the vaccines cannot be used for treatment after the onset of the influenza.
Therapeutic drugs for influenza are indispensable. Four anti-influenza drugs acting at either of two sites of action, namely, neuraminidase and M2 ion channel, are currently available, specifically, Oseltamivir (F. Hoffmann-La Roche Ltd., Switzerland), Zanamivir (GlaxoSmithKline, United Kingdom), Amantadine (Novartis International AG, Switzerland), and Rimantadine (Forest Laboratories, Inc., U.S.A.).
Only three of the above anti-influenza drugs are approved in Japan. However, the above-described drugs are not sufficient for a potential pandemic because of drug resistant strains and issues such as administration routes, a spectrum of influenza virus subtypes, and side effects.
Social concerns in development of a novel anti-influenza drug are extremely high. To take countermeasures against new strains and drug resistant strains, it is important to have multiple drugs which differ in structure and site of action. However, a novel drug which differs from existing drugs in structure and site of action has not been suggested, and is highly desired.
The onset of the influenza is caused by explosive replication of the influenza virus with symptoms such as inflammation and fever. Because the influenza virus infects the cells to replicate inside the cells, the explosive replication of the influenza virus is inhibited by blocking a life cycle of the influenza virus in any phase from binding of the influenza virus to the cell to budding and maturation of the influenza virus. A substance having the ability to block the life cycle of the influenza virus is highly promising as a substance having inhibitory activity against influenza virus replication and as an anti-influenza drug, capable of preventing the onset of the influenza or alleviating the symptoms of the influenza.
The present invention is researched and developed in view of the foregoing, and the present invention satisfies the expectations for the substance having inhibitory activity against influenza virus replication and the anti-influenza drug. An object of the present invention is to obtain wickerol that is a substance cultured using Trichoderma atroviride strain FKI-3737 (FERMABP-11099 corresponding to FERM BP-11099) and then isolated and purified from the culture, and also to provide a substance having inhibitory activity against influenza virus replication and containing the wickerol as an active ingredient, and an anti-influenza drug containing the wickerol as an active ingredient.